〔Abstract〕 Objective To observe the effects of a modified ketogenic diet on mice with a hyperuricemia(HUA) model and explore its mechanism of action. Methods Adenine and potassium oxonate were used to establish HUA model mice for in vivo experiments. The body mass and urine potential of hydrogen (pH) levels, blood glucose, total cholesterol (TC), triacylglycerol (TG), insulin resistance levels, and serum levels of uric acid (UA), blood urea nitrogen (BUN), and creatinine (CRE) were detected, and the expression levels of tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor type 1 (PAI-1), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in adipose tissue were also examined. Histopathological changes were observed, and the uric acid-lowering effect of a modified ketogenic diet with mulberry leaf water was investigated. Results The modified ketogenic diet was able to reduce body mass and serum levels of UA, BUN, and CRE, decrease the expression of pro-inflammatory adipokines in adipose tissue, and regulate urinary pH, as well as improve glycemic lipid levels, insulin resistance levels, and renal tissue injury in mice modeled with hyperbaric acid, as compared with the classical ketogenic diet. Conclusion The modified ketogenic diet of mulberry leaf water can effectively reduce the serum UA level in mice with hyperuricemia caused by adenine and potassium oxonate, and its mechanism of action may be related to the regulation of urinary pH, improvement of blood glucose, blood lipid level, and insulin resistance level, and reduction of pro-inflammatory adipokines expression.